ORIGINAL

Niger J Paed 2013; 40 (4): 400 – 405

Ibraheem RM

Johnson WBR

Abdulkarim AA

Abdulkadir MB

Oladele D

Serum zinc levels as a predictor of

clinical features and outcome of

paediatric acute lower respiratory

infections in Nigeria

Biliaminu SA

DOI:http://dx.doi.org/10.4314/njp.v40i4,10

Accepted: 19th May 2013

Abstract Background: Malnutri-

tion, especially macronutrient

deficiency, has been shown to be

interrelated with ALRI-related

morbidity and mortality. However

the import of zinc deficiency has

only recently become the focus of

research attention.

Objective: The current study was

carried out in Ilorin, Kwara State,

Nigeria to determine the relation-

ship between serum zinc levels,

clinical features and outcome in

hospitalized children with acute

lower respiratory infections

(ALRI).

tures (each p<0.05). Significantly

higher mean serum zinc level was

recorded in children with grunting

respiration compared with those

without grunting (p=0.028). Age-

related tachypnoea, grunting, and

crepitations remained significant

(each p<0.05) following a linear

regression analysis. The mean se-

rum zinc level in children with

multiple complications was sig-

nificantly lower than the corre-

sponding level recorded in chil-

dren who had one complication,

p=0.020. No significant difference

was found between the mean se-

rum zinc level of the children who

were discharged compared with

the corresponding level recorded

in those that died, p=0.589.

(

)

Ibraheem RM

Johnson WBR, Abdulkarim AA

Abdulkadir MB, Oladele D

Department of Paediatrics & Child

Health, University of Ilorin

Teaching Hospital, Ilorin, Kwara State,

Nigeria

P.O. Box 4564

Ilorin, Kwara State, Nigeria

E-mail: rasheedahbidmus@yahoo.com

Tel:+2348033704168,

+2348185415491

Biliaminu SA

Department of Chemical Pathology and

Immunology, University of Ilorin &

University of Ilorin Teaching Hospital,

PMB 1515, Ilorin, Kwara State,

Nigeria

Method:

A descriptive cross-

sectional hospital-based study

involving 120 children aged two

months to five years with ALRI.

Socio-demographic, clinical and

laboratory data were obtained.

The serum zinc was analyzed with

Conclusion: The presence of crepi-

tations had the strongest clinical

association with a low serum zinc

level. Children managed for ALRI

would benefit from post-treatment

zinc supplements and appropriate

zinc-rich sources of food at dis-

charge.

a

Jenway™ spectrophotometer

after initial preparation with the

QuantiChrom™ zinc assay kit.

Results: Children with tachypnoea

and crepitations had significantly

lower mean serum zinc levels

compared to the corresponding

values in those without these fea-

Keywords: Children zinc respira-

tory infections

Introduction

and other micronutrients has only recently become the

focus of research attention. Zinc is a trace element

which stimulates the activity of multiple enzymes in-

volved in various metabolic and immunologic responses

Malnutrition and acute lower respiratory infections

(

ALRI) are inter-related paediatric morbidities,

2

especially in the developing world. A recent WHO

in the body. This element is known to have a direct anti

report estimates that 6.9 million children under five

years of age died in 2011. About 80 percent of the

-viral activity and a demonstrabl₃e_-₄ effect on immune-

mediated production of interferon. Also, zinc prevents

pathogens from gaining entry_-₄into cells and hinders their

1

world’s under-five deaths in 2011 occurred in only 25

countries, and about half in only five countries including

Nigeria, which together account for more than a third of

3

intra-cellular multiplication. Zinc deficiency not only

decreases the ability of the body to respond to infection,

but also adversely affects both cell-mediated and hu-

1

under-five deaths worldwide. Globally, pneumonia is

3

one of the four major killers of children under age five

years. Whereas macronutrient deficiency has continued

to attract significant research interest, the import of zinc

moral immune responses. The current study was carried

out in Ilorin, Kwara State in the North Central region of

Nigeria to determine the relationship between the serum

4

01

zinc levels and clinical features in hospitalized children

with ALRI syndromes of bronchiolitis and pneumonia

as well as the outcome of the illness.

after adequate exposure. The presence of various clinical

signs such as nasal flaring, grunting, wheeze, and central

cyanosis were documented. Findings on percussion over

the intercostal spaces in the anterior and posterior chest

wall were recorded as normal, dull or hyper-resonant.

Auscultatory signs like the presence of diminished in-

tensity of breath sounds, crepitations, bronchial breath

sounds, and rhonchi were recorded. Other relevant

physical examination included identifying the presence/

absence of oedema, and skin changes such as peeling/

hypopigmentation around the perineum and acro-

orificial areas. Chest radiographs were obtained in all

subjects.

Materials and Method

This descriptive cross-sectional study was conducted in

the Emergency Paediatric Unit (EPU) and the Paediatric

Medical Ward of the University of Ilorin Teaching

Hospital (UITH), located in Ilorin South Local Govern-

ment Area (LGA) of Kwara State. Ilorin is the capital

city of Kwara State, situated in the North Central geopo-

litical zone of Nigeria.

Using strict aseptic techniques, two millilitres (mls) of

blood was collected via venepunture, aliquoted into a

plain bottle, and allowed to clot. Serum samples were

obtained by centrifuging the clotted blood sample at

3000rpm for five minutes in a bench-top centrifuge. The

sera obtained were transferred into sterile plastic tubes

5

Using the Fisher’s formula and a prevalence of 15.8 %

6

from a previous study, the minimum sample size of 102

was calculated but 120 subjects were recruited for ease

of analysis. Children aged between two months and up

to five years with an admission diagnosis of ALRI

o

and stored immediately at -20 C, till it was ready to be

analyzed when the sera were thawed followed by batch

analysis. Unhaemolyzed sera were used, and any serum

which was neither clear nor colourless was discarded

(

either pneumonia or bronchiolitis) were recruited and

followed up until discharge consecutively over a four

month period (April-July, 2010).

The serum zinc analysis was done with a Jenway™

spectrophotometer 6300 model (Jenway Limited, Dun-

mow, Essex, United Kingdom) for measuring optical

density at 425nm, after an earlier preparation with the

QuantiChrom™ Zinc colorimetric assay kit (B₂i₊oassay

Inclusion criteria included those with a diagnosis of

pneumonia based on the presence of acute cough, fever,

breathlessness, age-related tachypnoea and auscultatory

findings of one or more of reduced breath sound inten-

7

8

sity, bronchial breath sounds and crepitations. This was

Systems, Hayward, California, USA). The Zn Stan-

corroborated with the presence of patchy opacities in

one or more lobes, or lobar/ segmental consolidation

with or without the air bronchogram sign. Bronchiolitis

was diagnosed based on the presence of cough, fever,

wheezing and dyspnoea, associated with bilateral poly-

phonic expiratory rhonchi, inspiratory crepita₇tions and

clinical/radiographic features of hyperinflation.

dard (10µM), 50µl of water, Sample and Sample Blank

(50µL sample + 2µL EDTA) were transferred into wells

of a clear bottom 96-well plate. Subsequently 200µL of

8

the working reagent was added to each well and then

mixed by tapping the plate lightly. The resulting solu-

tion was allowed to incubate for 30 minutes at room

8

temperature. The optical density (OD) was read at 420-

8

4

26nm (peak absorbance at 425 nm). For this study, a

Exclusion criteria included children who had: received

any form of zinc supplementation in the preceding one

month, the severe forms of PEM (marasmus, kwashior-

kor and marasmic-kwashiorkor), sickle cell disease,

diarrhoea in the preceding one month, previously been

recruited for the study and representing with symptom

recrudescence.

Ethical approval was obtained from the ethical commit-

tee of the hospital. A semi–structured questionnaire was

administered to obtain the clinical data from the

caregiver after obtaining an informed consent.

value of 57µg/dl was used₉ as the lower cut-off for low

serum zinc concentrations.

Data was analysed using the SPSS 16 software package.

Frequencies, proportion, means and standard deviations

were calculated. The Student’s t-test was used to identify

significant differences for continuous variables. A linear

regression analysis was also done among the continuous

variables that were significant after the initial student’s

t-test.

Questions were asked on the presence/absence of

specific symptoms such as cough, fever, inability to feed

or drink, rapid or difficult breathing. The respiratory rate

was counted by observing each upward movement of the

abdominal/chest wall for one minute. Tachypnoea was

present if the respiratory rate was >50 breaths/min for

infants aged two months up to one year, and > 40

breaths/min for children aged 12-59 months. Chest wall

indrawing was identified as inward movement of the

lower chest wall on breathing in with the child lying flat

on either the caregiver’s lap, or the examination table

Result

Of 120 under-five children with ALRI recruited, 73

(60.8%) were male and 47(39.7%) and the male/female

ratio was 1.6:1. Forty-five (37.5%) of the children were

aged between two and < 12months, 30(25%) between 12

and < 24 months, 23(19.1%), 6(5.0%), 16(13.4%) be-

tween 24 and < 36 months, 36 and <48 months, 48

and<60 months respectively.

Nine (7.5) of the children had bronchiolitis, 16 (13.3)

4

02

lobar pneumonia and 95 (79.2) had bronchopneumonia.

The mean (SD) age of the ALRI subjects with bronchio-

litis was significantly lower than each of those with

bronchopneumonia and lobar pneumonia {8.1(5.9)

months versus 21.3(17.3) months, p=0.025; 8.1(5.9)

months versus 25.0(20.7) months, p=0.026 respec-

tively}. No such difference was identified between sub-

jects with bronchopneumonia and lobar pneumonia

Table 1: Serum zinc levels and the physical findings in chil-

dren with ALRI

Physical findings

Present

n (%)

Absent

n(%)

Serum zinc (µg/dl)

Dehydration

Mean(SD) Mean(SD)

62(51.7) 58(48.3)

6.7(8.6)

84(70.0)

t

p-value

1

20.8(14.3) -1.903

0.059

0.527

0.584

0.014

0.837

0.028

0.359

0.239

0.191

0.745

0.138

o

Fever(≥37.5 C)

36(30.0)

1

9.1(11.0) 17.6(13.7) 0.635

{

21.3(17.3) months versus 25.0(20.7) months,

Pallor

28 (23.3)

17.6(8.7)

112(93.3)

92(76.7)

19.0(12.6) -0.549

8(6.7)

p=0.444}.

Tachypnoea

Central cyanosis

Grunting

Overall, the mean (SD) serum zinc level recorded in the

children with ALRI was 18.7(11.8) µg/dl. The mean

17.9(11.7) 28.5(10.0) -2.503

8(6.7)

7.8(4.8)

14(11.7)

112(93.3)

18.7(12.2) -0.207

106(88.3)

1

(

SD) serum zinc level of 20.9 (15.5) µg/dl in children

with nasal discharge was significantly higher than the

corresponding value for those without nasal discharge of

2

5.2(21.1) 17.8(9.9)

2.228

Wheeze

4(3.3)

116(96.7)

4.0(1.62) 18.5(12.0) 0.920

101(84.2)

1

6.6 (6.5) µg/dl, p=0.046. The mean (SD) serum zinc

2

19(5.8)

level of 18.7(12.3) µg/dl in children with difficult

breathing was not significantly higher than the corre-

sponding value of 18.4(6.5)µg/dl in those without diffi-

cult breathing, p=0.931. No significant differences were

found on comparing the mean (SD) serum zinc levels of

the children with symptoms of vomiting, inability to eat/

drink, restlessness, lethargy with those without these

symptoms (each p=0.346,0.315, 0.521, 0.931 respec-

tively).

Snuffles

21.6(15.6) 18.1(11.0) 1.184

32(26.7) 88(73.3)

21.0(14.0) 17.8(10.9) 1.314

Rhinorrhoea

Nasal flaring

Inter-costal recession

98(81.7)

22(18.3)

1

8.5(12.6) 19.4(7.8)

-0.321

106(88.3)

14(11.7)

1

8.1(10.6) 23.1(18.7) -1.494

Lower chest wall

indrawing

69(57.5)

51(42.5)

1

7.9(11.4) 19.7(12.5) -0.821

115(95.8)

18.6(12.0) 0.203

94(78.3)

0.414

0.839

Table 1 shows the mean (SD) serum zinc levels based

on the physical findings in the children with ALRI at

presentation. Children with tachypnoea and crepitations

had significantly lower mean serum zinc levels com-

pared with those without these features (p=0.014 and

Head nodding

5(4.2)

9.7(6.0)

26(21.7)

1

Abnormal percussion

note

1

8.0(7.5)

18.8(2.8)

8(6.7)

-0.304

0.762

Reduced breath sound 112(93.3)

intensity

0

.003 respectively). Children with grunting respiration

had significantly higher mean serum zinc levels than the

recorded value in those without grunting (p=0.028).

18.4(12.2) 21.7(4.6)

102(85.0) 18(15.0)

7.3(10.5) 26.3(15.9) -3.066

-0.759

0.440

0.003

0.423

Crepitations

1

Crepitations +rhonchi 6(5.0)

114(95.0)

18.5912.1

)

The clinical features of age-related tachypnoea, grunting

respiration, presence of crepitations, remained statisti-

cally significant after a linear regression analysis

2

2.5(5.1)

0.803

Bronchial breath

sounds

11(9.2)

109(90.8)

(

7

Table 2). The goodness-of-fit model gave an F-value of

.116; df=4, p=0.001 and accounting for 19.8% effect

2

0.7(7.8)

44(61.7)

6.0(7.4)

18.5(12.2) 0.586

76(38.3)

20.2(13.6) -1.891

0.559

0.061

Hepatomegaly

on serum zinc levels. The presence of crepitations was

identified as the strongest clinical feature associated

with changes in the serum zinc levels in children with

ALRI.

1

A total of 46 complications were recorded in 35 (29.2%)

of the 120 children with ALRI; 24 (20.0%) had one

complication and 11(9.2%) children had more than one

complications. Figure 1 shows the overall distribution of

these complications, with heart failure as the single most

common complication.

Table 2: Linear regression analysis of some clinical parame-

ters of children with ALRI and their serum zinc levels

Parameter

Beta co-

efficient

0.327

t

p-value

Table 3 shows the mean (SD) serum zinc level in chil-

dren with more than one complication was significantly

lower than the mean level recorded in children who had

one complication (p = 0.020).

Nasal discharge

Age-related tachypnoea 0.180

Grunting

Dehydration

-0.092

2.099

-2.254

0.152

0.831

0.038

0.026

0.941

-0.195

0.103

0.310

0.748

Crepitations

3.667

0.001

0.919

Hepatomegaly

-0.030

4

03

these fe₁a₃_-t₁u₅res is in accord₁₃_-w₁₅ith those of some earlier

reports. These studies found that the children

Table 3: Relationship between complications of ALRI and

serum zinc levels

Variable

n(%)

Serum zinc level

(µg/dl) Mean(SD)

recruited as having ALRI based on the presence of

tachypnoea and crepitations had lower serum zinc lev-

els. Tachypnoea constitutes a valid avenue for an in-

crease in energy expenditure. This can be ascribed to the

increased work of breathing, higher insensible fluid loss

and a reduction in th₆ e food intake associated with the

t

p-value

Complication of ALRI

None

Present

85(70.8)

35(29.2)

18.0(12.8)

20.3(8.9)

0.964

0.337

Frequency of compli-

cation

One

More than one

24(68.6)

11(31.4)

22.6(9.4)

15.2(5.0)

1

2.444

0.020

respiratory distress. A combination of these tachyp-

noea-related phenomena could contribute to the low

serum zinc levels. The presence of crepitations in ALRI

probably reflects an ongoing inflammation in the lung

parenchyma. This inflammatory process associated with

pneumonia, and to a lesser extent in bronchiolitis, would

contribute to the lower serum zinc levels recorded in

subjects whom crep₃itations was identified as clinical

signs of pneumonia. The associated acute phase reac-

tion with the ongoing inflammation would also contrib-

ute to the lower serum zinc levels in those with crepita-

Fig 1: Complications among children with ALRI

combination

singly

8

17.4%)

(

2

1

(45.6%)

5

10.9%)

(

4

(8.7%)

3

(6.5%)

10

2

(4.3%)

tions. Also, the children may have had low pre-morbid

serum zinc level which was further aggravated by the

ongoing episode of ALRI.

3

(6.5%)

The current finding of higher serum zinc levels in chil-

dren with grunting respiration would appear to be incon-

sistent with an expectation of lower serum zinc levels in

ALRI subjects with grunting respiration premised on the

clinical import of the sign as an evidence of severe res-

piratory distress in severe pneumonia with or without

Seven (5.8%) children died while 113 (94.2%) had par-

tial or full recovery at discharge. Six (85.7%) of the fatal

cases were males, and one (14.3%) was a female. Of the

seven fatalities, four were infants while the remaining

three were aged above 24 months. Five of the children

that died had bronchopneumonia, and the other two had

lobar pneumonia. None of the children with a final diag-

nosis of bronchiolitis died. All the seven fatalities had

one or more ALRI-related complication.

7

associated pleural effusion. Although this finding ap-

pears superficially paradoxical, a plausible reason may

be the possible effects of this self-administered form of

achieving a peak end-expiratory pressure₆on the in-

1

trapulmonary vascular and tissue dynamics. By main-

taining a high intrapulmonary pressure and with the fre-

quent absence of tachypnoea, the high intrapulmonary

pressure may conceivably engender higher serum zinc

levels along with oxygen. In view of the current dearth

of published data to substantiate this finding, there is a

need for further studies with a larger sample size of chil-

dren with grunting respiration to validate the current

findings.

The mean (SD) duration of admission among the

survivors was 4.4 (2.3) days, while the corresponding

data among the fatal cases was 7.6(3.8) hours. Table 4

shows the relationship between the serum zinc levels,

the outcome of ALRI, and the duration of hospitaliza-

tion among both the survivors and the fatalities.

Table 4: The relationship between serum zinc levels and

duration of hospital stay among children with ALRI

The predominance of heart failure as a complication of

childhood pneumonia is consistent w₇i_,t₁h₀_,₁t₇he findings of

Variable

n(%)

Serum zinc level

(

µg/dl) Mean

SD)

t

p-value

earlier local hospital-based reports.

Heart failure

occurs due to the significant inflammation-driven reduc-

tion in the lung compliance associated with pneumonia

and resultant right ventricular strain. The identification

Outcome of ALRI

Recovery

113(94.2)

7(5.8)

18.8(12.1)

16.3(6.2)

0.541

0.589

7

Death

Duration of hospital stay

Among survivors (days)

of lower serum zinc levels in subjects with more than

one ALRI-related complication compared with the cor-

responding values in those without would suggest a zinc

lowering effect of these complications. This may be

related to the defective leucocyte phagocytic action due

to zinc deficiency, with resultant failure to hinder intra-

≤

4

80(69.0)

43 (17.7)

19.8(3.7)

16.6(6.9)

1.423

-

0.158

0.502

>

4

Among fatality (hours)

≤

8

5(71.4)

2(28.6)

15.2(6.8)

19.1(4.5)

0

.722

>

8

3

cellular multiplication of pathogens, and the subse-

quent unfettered dissemination of pathogens causing

widespread damage and complications.

Discussion

The case fatality among the children with ALRI in this

series was 5.8% which is lower than the 7.8% recorded

by Johnson et al in Ibadan, and the value of 10.0%

The findings of lower serum zinc levels in children with

tachypnoea and crepitations compared to those without

7

4

04

identified in an earlier study by Fagbule et₀al in Ilorin

paucity of published data to compare with would hardly

enable this author to draw firm inferences from this ob-

servation. Also, the pre-morbid serum zinc levels of the

children recruited were not determined in the current

study. Hence, more studies would be required in future

to determine the trend of changes in serum zinc levels

with regard to the disease outcome of ALRI in children.

1

where the present study was carried out. The corre-

sponding values from other cou₁n₈tries included the

1

5.0% reported by Nathoo et al in Zimbabwe and

19

0.5% by Seghal et al in India which were also higher

than the recorded value in the present study. The small

decrease over the years in ALRI-related mortality may

be possibly ascribed to a more prompt home recognition

of disease severity, early diagnosis, better defined crite-

ria for referrals, as well as the institutional adoption of

more ₁e₉f_,₂f₀ective management strategies in the last few

Conclusion

years.

About 70% of the fatal cases were accounted

for by bronchopneumonia, thus constituting the single

most important contributor to ALRI case fatality in the

current study. This observation is in accord with the

earlier reports e₆m_,₇a_,n₁₀a_,t₂i₁ng from South-West and North-

The presence of crepitations had the strongest clinical

association with a low serum zinc level. No significant

difference was identified between the mean serum zinc

level of the children who recovered and those that died.

Children managed for ALRI would likely benefit from

post-treatment zinc supplements and appropriate zinc-

rich sources of food at discharge.

Central Nigeria,

as well as those from other de-

1, 18

However, the import of this ob-

1

veloping countries.

servation is difficult to ascertain in view of the fact that

bronchopneumonia was the most common admission

diagnosis, accounting for almost 80.0% of the ALRI

syndromes diagnosed at recruitment.

Authors contribution: All authors contributed to the

study protocol, data collection, data analysis.

Ibraheem RM: did the final draft of this paper.

Conflict of interest: None

There was a paucity of published studies documenting

the relationship between the serum zinc levels and out-

come in children with ALRI for comparison however,

the present study found that neither the duration of hos-

pitalization nor the outcome of admission were signifi-

cantly affected by the serum zinc levels. This might be

due to a limitation in the number of cases analyzed for

this outcome variable. It is however of clinical signifi-

cance as survivors with longer hospital stay had lower

zinc levels while lower serum zinc levels were identified

in those with a shorter hospital stay among the fatal

cases. One or more ALRI-associated complication was

identified among all cases with a fatal outcome, thus

suggesting a zinc lowering effect with increased severity

of ALRI and related complications. However, the

Funding: None

Acknowledgement

All the consultants, residents and entire nursing staff of

the EPU are acknowledged. Dr. Jimoh K, Consultant

Radiologist is also acknowledged for his contribution.

Indeed, authors are indebted to the parents who con-

sented to be part of this study.

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